According to results from a cohort study published recently in JAMA Pediatrics, pediatric patients who received recombinant human growth hormone (rhGH) had at an expanded risk of cardiovascular events once they reached early adulthood. In this study, Tidblad et al explored the long-term risk of overall and severe cardiovascular events in patients previously treated with rhGH in childhood to ascertain if there is a correlation with treatment duration or dose.

In this study from Sweden, patients were followed up for 25 years. The population-based cohort study included patients treated with rhGH during childhood from January 1, 1985, to December 31, 2010, with follow-up through December 31, 2014. Patients were treated with rhGH due to isolated growth hormone deficiency (GHD), being small for gestational age (SGA), and idiopathic short stature (ISS). For each patient, 15 age-, gender-, and region-based, matched controls were randomly chosen from the general population as a comparison group. Data on cardiovascular outcomes and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height were obtained via several healthcare- and population-based registers.

The researchers found that a total of 53,444 individuals (3,408 patients and 50,036 controls; 67.7% men; average [standard deviation] age at study end, 25.1 [8.2] years) were followed up for as long as 25 years (average follow-up, 14.9 [range, 0-25] years; total, 795,125 person-years). Among 1,809 recorded cardiovascular events, the crude incidence rates were 25.6 events per 10,000 person-years for patients and 22.6 events per 10,000 person-years for controls.

The adjusted hazard ratio (HR) for all cardiovascular events was greater in patients compared with controls (HR, 1.69; 95% CI, 1.30-2.19), especially for women (HR, 2.05; 95% CI, 1.31-3.20) compared with men (HR, 1.55; 95% CI, 1.12-2.13). All subgroups had expanded HRs (SGA, 1.97 [95% CI, 1.28-3.04]; GHD, 1.66 [95% CI, 1.21-2.26]; and ISS, 1.55 [95% CI, 1.01-2.37]). Longer duration of rhGH treatment (HR, 2.08; 95% CI, 1.35-3.20) and total cumulative dose (HR, 2.05; 95% CI, 1.18-3.55) were correlated with elevated risk for overall cardiovascular disease.

The adjusted HR for severe cardiovascular disease was 2.27 (95% CI, 1.01-5.12). The researchers concluded that in this cohort study, treatment with rhGH during childhood due to GHD, SGA, or ISS was linked to heightened risk of cardiovascular events in early adulthood, especially in women; however, conclusions of causality are still inadequate, and the absolute risk remains low.

The authors noted, “Differences in estrogen levels or responsiveness to rhGH treatment have previously been hypothesized as possible explanations, but the underlying mechanism for this gender difference still remains unclear and merits further investigation.”

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to Cardiology Update.